Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study By UCSD Researchers Gives New Insight Into How Anthrax Bacteria Can Evade A Host’s Immune Response

07.01.2004


Biologists at the University of California, San Diego have determined how toxin produced by anthrax bacteria blocks a person’s normal immune response, a discovery that could lead to new treatments for anthrax infection.



In a paper to be published in the January 15th issue of The Journal of Immunology the UCSD scientists show why, in the presence of anthrax toxin, human immune cells fail to respond normally to lipopolysaccharide—a component of the cell walls of many bacteria including the bacteria that cause anthrax, Bacillus anthracis. Bacterial invasion, or the presence of lipopolysaccharide, usually causes immune cells known as macrophages to release cytokines—chemicals that signal other cells about the presence of an invader. Release of cytokines causes large numbers of immune cells to arrive at the site of infection and destroy the bacteria. By blocking this host immune response, anthrax bacteria are able to multiply unchecked. According to the Centers for Disease Control, approximately 75 percent of people infected with inhalation anthrax die, even with all possible supportive care including appropriate antibiotics.

“Although it was known for quite some time that anthrax toxins can suppress cytokine production, the mechanism by which Bacillus anthracis escapes the immune response isn’t really understood,” says Michael David, a biology professor at UCSD who headed the research team. “We have identified a protein molecule targeted by the anthrax toxin and determined where it acts in the sequence of steps involved in immune response.”


Macrophages have special receptors on their surfaces that bind to lipopolysaccharide. The binding of lipopolysaccharide to this receptor sets off a sequence of events inside the macrophage, in which a series of proteins activate one another in turn. This cascade of proteins activating one another ultimately turns on cytokine genes, causing the macrophage to churn out large quantities of cytokines.

It turns out that there are two separate, sometimes cooperating, routes in the cell by which series of proteins activate one another to switch on production of cytokines. One of the routes has been recognized for a long time, but researchers were sometimes puzzled when cytokine production was turned on or off without the proteins along this route being activated or deactivated. This puzzle was resolved when the David group and other groups simultaneously identified the second route, the IRF3 pathway. The anthrax toxin targets the IRF3 pathway by cleaving MKK6—one of the proteins in the series along the route. The cleavage of MKK6 prevents the cytokine genes from being switched on.

When the researchers made mutant macrophages with a variant of MKK6 that could not be cleaved by the anthrax toxin, these macrophages responded to lipopolysaccharide by producing cytokines even in the presence of the anthrax toxin. This suggests that developing a drug that could protect MKK6 and prevent anthrax toxin from cleaving it could help to prevent an anthrax infection from getting out of control. The anthrax bacteria would be unable to evade the normal immune response.

“While these results may not lead to a drug to cure anthrax in the next six months, the more you understand about bacteria and how they target the immune response the more options you have for developing drugs to treat the infections,” says David.

Previous work by other researchers has suggested that anthrax toxin evades the immune system by killing macrophages; however, according to David, cell death does not fully explain how anthrax bacteria evade the immune system.

“Only some types of macrophages are killed by anthrax toxins, but anthrax toxins diminish the production of cytokines in all of the macrophages we have tested,” David explains. “Also, less toxin is needed to shut off the immune response than to kill the macrophages.”

The other UCSD researchers involved with this project were Oanh Dang, a former graduate student in the David laboratory and the first author of the paper; Lorena Navarro, a former graduate student in the David laboratory and first author on two other papers that initially identified the IRF3 immune response pathway; and Keith Anderson, a technician in the David laboratory. This work was supported by a grant from the National Institutes of Health.


Media Contacts: Sherry Seethaler (858) 534-4656
Comment: Michael David (858) 822-1108

Sherry Seethaler | UC - San Diego
Further information:
http://ucsdnews.ucsd.edu/newsrel/science/santhrax.asp

More articles from Life Sciences:

nachricht Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg

nachricht Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Polymers Based on Boron?

18.01.2018 | Life Sciences

Bioengineered soft microfibers improve T-cell production

18.01.2018 | Life Sciences

World’s oldest known oxygen oasis discovered

18.01.2018 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>